INHERITED DISORDERS OF CATTLE: A SELECTED REVIEW

Arcangelo Gentile 1*, Stefania Testoni 2

Addresses of authors: 1

Veterinary Clinical Department, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano dell’Emilia,

Bologna; 2

Department of Veterinary Clinical Science, University of Padova, Via dell’Università 16, 35020, Legnaro Padova, Italy

* Corresponding author, E-mail: arcangelo.gentile@unibo.it

Abstract: In this paper, the authors summarize the characteristics of the most important inherited disorders they have

encounteredfirst hand.

For some of the diseases discussed, the genetic origin has been definitively stated. For others, it is still only a hypothe-

sis which has yet to be confirmed. For all of them, the authors emphasize the importance of identififying and reporting them

to diagnostic centres. At the moment in Italy, the authors are trying to develop a program to identify carriers of an unde-

sirable pathological character and to increase relative clinical and pathological knowledge.

Key words: hereditary diseases; central nervous system diseases – genetics; skin diseases – genetics; bone diseases –

genetics; cattle

Received: January 2006

Accepted for publication: Fabruary 2006

Slov Vet Res 2006; 43 (1): 17-29

UDC 619:616-056.7:636.2

Introduction

Strong inbreeding in the bovine population hasincreased the risk of the occurrence of geneticdiseases. In fact, the wide use of only a few elitesires has enhanced the probability of the couplingof two mutated recessive genes in the genotype ofan animal.

One of the most important problems in con-trolling the genetic diseases is that, once the dis-order has finally been discovered, the allelic fre-quency of the recessives might have alreadyreached high values in the population of theaffected breed. In fact, it usually turns out that agenetic disease reveals itself many years after themutation has occurred, corresponding to the timethat the male and female descendants of the orig-inal carrier are mated. In the meantime, the allelemight have been widely spread throughout thebovine population.

For this reason it is very important that, asearly as possible, the phenotype associated with aphysiological abnormality, biochemical defect orenzyme deficiency be attributed to a mutatedhomozygous genotype.

Conditions alerting the investigator to the factthat an abnormality is likely genetic in nature are:1) it is more common in a group of related ani-

mals;2) it is observed during all seasons of the year

and in different geographic locations;3) it appears more frequently as the level of

inbreeding increases.Whatever the causes, the first step in reducing

the incidence of any defect is an accurate clinicaland pathological description. The reporting and,possibly, the referring of any suspected case todiagnostic centres is therefore an indispensablestep towards improving the possibility of recogni-tion. At the moment in Italy, we are trying todevelop a program to identify the carriers of anundesirable pathological character and toincrease relative clinical and pathological knowl-edge so that future cases can be better diagnosedand possibly prevented.

This paper reviews the characteristics of themost important inherited disorders we haveencountered first hand. The diseases discussedare classified according to the principal body sys-tem affected.

Bibliographic references are limited to part ofthe papers related to genetic diseases written bythe authors together with the most significantand recent articles in the literature.

Review Paper

A. Gentile, S. Testoni18

Inherited central nervous system diseases

Spinal Muscular Atrophy (1, 2, 3, 4, 5, 6, 7)

Spinal Muscular Atrophy (SMA) is a progres-sive lethal disease reported mainly in advancedbackcrosses between American Brown-Swiss andEuropean Brown cattle breeds but also describedin Holstein-Friesian calves. It represents the mostworrisome concern for Brown breeders’ associa-tions.

The condition is characterized by severe muscu-lar atrophy, progressive quadriparesis, and sternalrecumbency. The initial signs - symmetric weak-ness of the rear legs, locomotive difficulties andslight dyspnoea - appear at 3-4 weeks of age. Thecourse of the disease is progressive, and the calvesbecome increasingly weaker and progress to para-paresis and finally tetraparesis (Fig. 1). Animalsusually look alert and have a good appetite and anormal suckling reflex. Urination and defecationare in the physiological range. The symptoms arequite similar to white muscle disease (nutritionalmuscular dystrophy). Death occurs after 2-4weeks, usually as a consequence of respiratory fail-ure due to atrophy of the respiratory muscles.Occasionally, calves are unable to stand up fromthe moment of birth. Histo-pathologically, the con-dition is mainly characterized by muscle fibre atro-phy and axonal degeneration of the spinal cord aswell as neuronophagia and degeneration and lossof motor neurons in the grey matter of the ventralhorns (especially in the brachial and lumbo-sacralregions); furthermore, severe vacuolar degenera-tion in the midbrain and central motor cortex canbe observed. Neuron degeneration seems to origi-nate in unrestrained apoptotic processes initiatedduring foetal development.

Bovine-SMA is inherited as an autosomalrecessive disorder and its gene has been mappedto the distal part of Chromosome 24. Most of thecases reported can be traced back to an AmericanBrown Swiss bull named “Meadow View Destiny”.

At present, marker-assisted tests are availablein order to detect carriers of this undesirablegene.

Spinal Dysmielination (8, 9, 10, 11,12, 13)

Spinal Dysmielination (SDM) is another con-genital and genetic neurological disorder mainlyaffecting Brown or cross-bred calves upgradedwith American Brown Swiss.

Affected animals have congenital recumbency(contrarily to SMA) and, for the most part, lie in alateral position with a slight to moderateopisthotonos (Fig. 2). Rear limbs are held in exten-sion and. on pressuring the interdigital skin, theyreact by stretching or kicking. The hind limbs alsoremain typically extended if calves are able tomaintain the sternal position. Although the ani-mals do not try to rise, they are attentive to theirsurroundings. Main reflexes, appetite, faeces andurine delivery are normal. Affected calves usuallydie or are euthanized during the first week of life.

Histopathologically, the disorder is mainlycharacterized by bilateral symmetrical dysmieli-nation in the white matter of the spinal cord(gracile funiculus, dorsolateral spinocerebellartract, sulcomarginal tract), especially at the levelof cervical intumescence. Typically, the sub-meningeal areas have a more pronounced dys-mielination than the deeper parts. Moreover, thenumber of axons within the affected tracts isreduced. Myelination of the dorsal and ventralnerve roots appears normal.

Figure 1: Two-week-old Brown calf affected by SpinalMuscular Atrophy; the calf is weak and not able tomaintain the quadrupedal stance. Forelegs are typical-ly maintained extended forward. Note the muscularatrophy of the hindquarters

Figure 2: Two-day-old Brown calf affected by SpinalDysmielination; the calf is lying in a lateral positionwith opisthotonus

Inherited disorders of cattle: A selected review 19

Similarly to bovine-SMA, SDM is an autosomalrecessively-inherited defect. There is evidencethat SDM might be traced back to an AmericanBrown Swiss bull named “White Cloud JasonsElegant” born in 1966.

A marker-assisted test based on five markershas recently been developed in order to detect car-riers of this undesirable gene. It is however limit-ed to some genetic lines.

Bovine Progressive Degenerative Myeloencepha-

lopathy (“Weaver” Syndrome) (14, 15, 16)

Bovine Progressive Degenerative Myeloence-phalopathy (BPDM) is an inherited disorder ofpurebred Brown cattle characterized by progres-sive bilateral hind leg weakness and ataxia,resulting in a weaving aspect of the gait.

Clinical synptoms become apparent at about6-8 months of age and slowly increase in severityuntil the animals become unable to rise. Paresisand ataxia are due to proprioceptive deficitsinvolving all four limbs, although the hindlimbsusually appear worse than the forelimbs. Ifturned quickly or stimulated to run, thehindquarters tend to lose balance and the ani-mals fall laterally (Fig. 3). The same happens iflateral pressure is applied anywhere above the sti-fle or at the level of the hip. The deficit increasesslowly in affected animals and invariably becomesrecumbent.

Histopathologically, the lesions are character-ized by axonal degeneration and vacuolation ofthe white matter of the spinal cord and degenera-tive changes or numeric reduction of the Purkinjecells in the cerebellum.

The U.S. sire “Nakota Destiny Dapper” and itssons “Target” and “Matthew” were responsible for

the diffusion of BPDM. The defect has beenmapped through linkage analysis to bovineChromosome 4. A strong selective advantage formilk production has been demonstrated in BPDM-carriers. This was the reason which caused theincrease in the frequency of the defective gene. Anofficial DNA marker test allows control of the genefrequency effectively enough, without removingidentified BPDM-carriers from service.

Spastic Paresis (17, 18, 19, 20, 21, 22)

With the term Spastic Paresis, we recognize asporadic neuromuscular disease of cattle clinical-ly characterized by a hyperextension of the rearlimbs (“straight hock”) due to a contraction of themuscles which form the Achilles tendon (Fig. 4).Signs of Spastic Paresis usually appear at the ageof 3 to 8 months, although these signs mayappear when the calves are only a few weeks oldas well. More unusual are the cases of lateronset, as late as 3 years (Fig. 5).

Figure 3: Eighteen-month-old Brown heifer affected by“Weaver syndrome”; stimulated to run, the animaltends to lose balance and falls laterally

Figure 4: Seven-month-old male Romagnola animalaffected by Spastic Paresis; note the hyperextension ofthe hock and the “pendulum” movement of the righthind limb

Figure 5: Six-year-old Holstein cow affected by SpasticParesis; the left hind leg remains completely raised fromthe ground and extended backwards

A. Gentile, S. Testoni20

In the initial stage, the most remarkable find-ing is the hyperextension of the hock with anincrease of the tibiotarsal angle (“straight hocks”).The condition has a progressive but not pre-dictable course over a period of a few weeks ormonths; the straightness of the limb becomemore severe and the calcaneus tends to be drawnto the tibia so that it is possible to observe a wrin-kling of the skin corresponding to the distal partof the Achilles tendon. The stifle can however beeasily flexed and, in this way, tremulous contrac-tions and further rigid extension of the limb canbe provoked. The affected animal has a stiff gaitand moves without normal hock flexion.

Later on, the leg is held so that the foot justtouches the ground with the toe or it remainscompletely raised from the ground and extendedbackwards. In these cases, the animal uses onlythree legs to walk; the severely affected leg is heldpermanently in extension and contractural fitscause a typical “pendulum” movement, with mostmotion occurring at the coxofemoral joint. Thissign is most evident immediately after standingup when it is also possible to observe an archingof the back and elevation of the tailhead.

In the majority of cases, only one leg is affect-ed: if both limbs are involved, the animal bearsweight alternatively on each leg.

It is worth noting that, in recumbency, the ani-mal is completely normal. Moreover, the tone ofthe affected muscles is normal as has been con-firmed by electromyographic studies.

Spastic Paresis is caused by a spastic contrac-tion of the antigravitational, foot extensor musclegroup, especially the gastrocnemius and thesuperficial digital flexor. Other muscles such asbiceps femoris, semitendinosus, semimembra-nosus, quadriceps femoris and adductor musclescan also be involved. The contraction of thequadriceps femoris characterizes the recentlydescribed atypical form of Spastic Paresis of thefemoral quadriceps, first observed in BelgianWhite Blue calves but then also observed inRomagnola animals. In these cases, the affectedhind leg shows a swaying movement in anteriordirection.

The muscular spasticity should be attributedto hyperactivity of the myotatic reflex (“stretchreflex”). The dysfunction lies primarily in thegamma-pathway which means in an anomalousaction of the gamma-motor neurons. On the basisof this pathogenetical hypothesis, it is neverthe-less still unknown whether the overstimulation ofthe gamma-pathway is due to intrinsic hyperac-tivity of the gamma-motor neuron or to a lack ofinhibitory mechanisms; in the latter case, a defect

of the regulatory descendant pathway arisingfrom the red nucleus (rubrospinal pathway) orfrom the lateral vestibular nucleus (vestibu-lospinal pathway) could play an important role.

Although the hereditary contribution appearsunquestionable, up to now, it has not been possi-ble to definitively determine the mode of inheri-tance (dominant or recessive) or the entity of pen-etrance of the single or multiple genes responsi-ble. It is supposed by most authors that the modeof inheritance could be recessive with low orincomplete penetrance. It should therefore beassumed that environmental (plant toxicity?),nutritional (trace element deficiency = Mn, Ca, P,Cu, Zn, Co, I, Se?; vitamin deficiency = vit. A?),metabolic (Cu/Zn imbalance?) or individual fac-tors can play an important role in the appearanceand expression of the disease.

Many types of therapy have been suggested,including tenotomy of the gastrocnemius tendonand neurectomy of the branches of the tibialnerve supplying the gastrocnemius muscle. Ourexperience is limited to the total neurectomy ofthe tibial nerve which has shown interestingresults but not a complete recovery.

Spastic Syndrome (23, 24, 25)

Spastic Syndrome (“crampiness”, “Krämpfi-gkeit”) is a chronic condition occurring in adultcattle. It is a particular problem in the maturebulls maintained in artificial insemination cen-tres but can also affect cows in a recurrent or ina progressive form. Animals of several breeds canbe affected. The disease is characterized by inter-mittent bilateral spasms of the skeletal muscles ofthe pelvic girdle, including the muscles of therump. Each spasm is accompanied by kyphosiswhich is often terminated by a tremor of thehindquarters (Fig. 6). During the attack, one hind

Figure 6: Three and a half-year-old Holstein cow affectedby Spastic Syndrome; note the kyphosis

Inherited disorders of cattle: A selected review 21

leg (usually always the same) may lift laterally inpartial flexion. The intensity and duration of thespasms progressively increase over time.

There is a paucity of literature on SpasticSyndrome and the few reports which includedmorphological examinations failed to reach signif-icant results and concluded that the syndrome isa type of idiopathic or true muscle cramps.

Regarding the aetiology, there is evidencewhich suggests a recessive mode of inheritancebut with incomplete penetrance.

There is no specific treatment for the condi-tion; we personally recommend the use of anal-gesic drugs.

Inherited congenital skeletal malformations

Craniofacial defects

Some of the literature lists closure defects ofthe lip (cleft lip) and/or the palate (cleft palate –Fig. 7) as genetic defects, likely polygenic, butmore data are needed to confirm this hypothesis.In any case, it should be mentioned that thesefacial defects (especially cleft palate) constitute arelatively frequent congenital anomaly which maybe part of a complex congenital malformations invarying degrees.

Another relatively common, more or less pro-nounced, congenital anomaly is short lower jaw(brachygnatia). Also for this defect, an inheritedorigin is suggested, especially for Simmentalsand, more recently, Brown breeds.

Chondrodysplasia and “ Congenital Paunch

Calf Syndrome” (26, 27, 28, 29, 30)

Chondrodysplasia is a disturbance of endo-chondral ossification leading to disordered bonedevelopment. Although several types of chon-

drodysplasia are known, the most common formin Italy is the so-called “Bulldog calf” of theRomagnola breed (Fig. 8). It is characterized by aflat head with a short nose and sloping foreheadand by short and stumpy limbs. Severe affectedcalves live only a few months.

The bone growth disturbances involve a defectof cartilage growth which hinders the normallengthening of the long bones. The chondrocytesdo not undergo physiological differentiation sothey cannot fulfil normal endochondral ossifica-tion in osteogenesis.

More recently, we have reported another formof achondroplasia in Romagnola calveswhich wehave called “Congenital Paunch Calf Syndrome”because, besides facial defects, another mainclinical feature is abdominal distension and alsobecause this is the name used by farmers whenthey report the affected animals.

Facial deformities are characterized by a short-ened and flattened face and, in some cases, by anenlarged head. contrarily to other achondroplas-tic defects, in this case, limbs only rarely show adisproportionate shortness. Cleft palate is a fre-quent accompanying finding.

The most characteristic symptom of thesecalves, however, is an enlarged and floatingabdomen, denoting considerable abdominal effu-sion (Fig. 9). Moreover at necropsy, the animalsusually show marked subcutaneous oedema,especially in the ventral part of the abdominalwall. Different quantities of ascitic fluid (in somecases up to 10 litres) are present in the abdomi-nal cavity. The liquid ranges from yellow to red,with different grades of turbidity.

Another characterizing aspect is moderate tosevere diffuse hepatic fibrosis, associated with thepresence of hepatic cysts, containing serous orreddish fluid. Microscopic examination of theliver reveals an extensive distortion of lobular

Figure 7: 40-day-old calf affected by cleft palate

Figure 8: Six-month-old Romagnola animal affected byachondroplasia; note the facial deformity

architecture by widespread fibrosis in periportalareas and around the centrolobular veins. Insome lobules, the fibrosis extends to the perisi-nusoidal spaces.

Cardiac malformations, such as atrial andinterventricular septal defects, and patent ductusarteriosus can be observed.

At the moment, we have not found any familialline which can be considered responsible for theinheritance of the defect; nevertheless, a geneticcause is strongly suspected.

Complex Vertebral Malformation (31, 32, 33, 34,35, 36, 37, 38, 39, 40, 41)

At present “Complex Vertebral Malformation”(CVM) represents the most worrisome hereditaryconcern for Holstein breeders. This defect is clin-ically characterized by the following phenomeno-logical triad: (a) reduced body size; (b) symmetri-cal arthrogryposis; (c) malformations in the cervi-cal and/or thoracic vertebral column (especiallyshortened neck and scoliosis). Homozygous ani-mals usually die during pregnancy, are prematureor stillborn, or die shortly after birth. Besides theaforementioned clinical triad, live calves might bealert and show a suckling reflex and appetite.They are unable to stand up (Fig. 10), lying downin a flat position with extended limbs (frog-likedecubitus).

Clinical diagnosis is confirmed by radiograph-ic examination of the vertebral column whichshows multiple vertebral anomalies includinghemivertebrae, fused and misshapen vertebraeand ribs, and scoliosis affecting mainly the cau-dal cervical and the thoracic regions (Fig. 11).

A complex malformation of the heart, charac-

terized by atrial and/or interventricular septaldefects, and patent ductus arteriosus mightaccompany the skeletal malformations.

CVM stems from a simple autosomal recessiveallele which can be detected by a DNA-PCR basedtest.

Interesting recent analysis has demonstratedthat a different expression of the foetal CVM phe-notype might directly influence several fertilitytraits, such as non-return rates for cows, calving

A. Gentile, S. Testoni22

Figure 9: Stillborn Romagnola calf affected by the so-called “Congenital Paunch Calf Syndrome”; note theenlarged and floating abdomen (denoting a consider-able abdominal effusion) and the facial deformities(shortened and flattened face)

Figure 10: Two-day-old Holstein calf affected by ComplexVertebral Malformation; despite repeated attempts tostand up, the calf is unable to do so. If supported byassistants, its feet rest on the dorsolateral face of thepastern on the ground; the head hangs down betweenthe forelimbs

Figure 11: X-ray and anatomical dissection of the samecalf as in Fig. 10 = on the left: note the presence ofhemivertebrae in the thoracic (T1, T2, T7, T8) and lum-bar (L2) regions; on the right: note the evident S-shapeddeviation of the vertebral column at the level of the tho-racic and lombar tracts (scoliosis)

Inherited disorders of cattle: A selected review 23

frequency after a first insemination and the inter-val between insemination and the next calving;according to recent research, 16% of CVM-affect-ed embryos die within the first 56 days of preg-nancy, and up to 45% and 77% of CVM-affectedfoetuses die before the 150th and the 260th gesta-tion-day, respectively. The frequency of calvingresulting in a live-born calf 260-300 days afterfirst insemination has been calculated to bereduced by 93% if the foetuses had the CVM phe-notype, therefore deducing that only 7% of CVM-affected calves survive the gestation period.

Unless the malformation is severe, the verte-bral defect might be overlooked during routineexamination of the aborted foetuses or stillborncalves, and the same may be said of neonatesapparently affected by only arthrogryposis andincapable of assuming the quadrupedal stance.

The embryonic/foetal mortality rate might alsobe biased by the observed rate of heat, the cullingof pregnant cows and embryonic/foetal mortalitywithout any connection to CVM. All these situa-tions negatively influence the perception of thepresence of the defect in the herd and, therefore,do not allow the exact estimation of the economicloss related to foetal and near-term deaths asso-ciated with the defect.

Retrospective evaluation of the familial occur-rence has demonstrated that the former elite U.S.Holstein Carlin-M-Ivanhoe Bell should be consid-ered one of the biggest spreaders of the disease. Itvery probably received the defective allele from itsfather, Penstate Ivanhoe Star. It should be men-tioned that the same family of sires has been rec-ognized as te carrier of another recessive genedefect, Bovine Leukocyte Adhesion Deficiency(BLAD). However, the two gene defects are notlinked and are inherited independently.

Arachnomelia (42, 43, 44, 45, 46, 47, 48, 49)

Arachnomelia (“spider-legs”) is a congenitalabnormality of the skeletal system giving the ani-mal a spidery look, and reported both inSimmenthal and Brown calves.

The most important pathologic findings are:facial deformities (i.e. brachygnatia inferior andconcave rounding of the dorsal profile of the max-illa), bone dolichostenomelia, angular deformitiesin the distal part of the hind legs (Fig. 12), mus-cular atrophy and cardiac malformations. Thebones of the legs appear to be more fragile thannormal and spontaneous fracture during calvingmay injure the dam.

Although we failed to find precise informationin the literature, the pathogenesis of the disease

seems to overlap that of Marfan Syndrome inhuman medicine (Arachnodactylia); in this con-text, a defect in the metabolism of the connectivetissue is involved. However, the clinical findingsrecorded in calves affected by Arachnomelia usu-ally differ from the typical picture of human“Marfan patients” (dolichostenomelia with highfragility of the long bones, defects of the heart andmain arteries and ectopia lins) and, for this rea-son, we think that the clinical identificationbetween bovine Arachnomelia and human MarfanSyndrome is inappropriate. Moreover, contrary tothe almost undisturbed vitality of humanpatients, bovine Arachnomelia has a rapidlylethal course.

It should be kept in mind that true BovineMarfan Syndrome, more closely resemblinghuman Marfan Syndrome, has also beendescribed in cattle.

As far as the aetiology is concerned, althoughit has not been possible to find candidate genesuntil now, the condition is attributable to a sim-ple autosomal recessive inheritability. The U.S.sire “Novic Lilasons Beautician” was responsiblefor the diffusion of the defect . At the moment,there is neither a chromosomal nor a biochemicaltest to detect the carriers of this defect.

Short Spine Lethal (50, 51, 52, 53, 54, 55)

Short Spine Lethal is a rare skeletal malforma-tion externally characterized by a marked anddisproportionate shortening of the vertebral col-umn associated with a normally developed headand legs (Fig. 13). Shortening of the neck might bevery pronounced giving the impression that thehead is fixed to the chest. Misalignment of theteeth and mandibular hypoplasia, resulting in

Figure 12: Stillborn Brown calf affected by Arachno-melia; note the abnormal length and thinning of all legs(dolichostenomelia). Forelegs show severe angulardeformities in their distal part

A. Gentile, S. Testoni24

protrusion of the tongue from the oral cavity,might be observed. Despite being full term, calvesmight present a strong reduction in body weight.

External conformation is due to several spinalmalformations, including fusion and/or varia-tions in the number of vertebrae, abnormal verte-bral body size and shape, and misalignment ofvertebral segments, mainly involving the cervicaland thoraco-lumbar tract.

Visceral malformations involving the urogeni-tal, gastrointestinal, and cardiovascular systemsmay also be found.

In all cases published, the occurrence of com-mon ancestors has suggested a genetic aetiology.Unfortunately, due to the limited number ofcases, evaluation of the mode of inheritance is dif-ficult.

Perosomus acaudatus/elumbis (56, 57, 58, 59)

Partial agenesis of the vertebral column consti-tutes a relatively common occurrence and can belimited to the coccygeal tract (Perosomus acauda-tus, Brachyury) or also involve the sacral and/orlumbar tract (Perosomus elumbis). Although evi-dence of inheritance has been reported in thepast, more information is needed to confirm thegenetic hypothesis.

The simple lack of the coccygeal vertebrae(Perosomus acaudatus) is compatible with lifeand animals can also carry out pregnancy with-out any problem. In more extended failures of ver-tebral development (Perosomus elumbis), theback of the lumbosacral region lacks a rigid skele-tal support, and the hindquarters, stronglyunderdeveloped and possibly paralyzed, arelinked to the rest of the body only by soft tissue.In these cases, calves are shorter than normaland cannot maintain a quadrupedal stance oruse their hind legs at all (Figs. 14 and 15).

Figure 13: Stillborn Holstein calves affected by ShortSpine Lethal. In both animals the trunk was dispropor-tionately short for the body size and legs. Note themandibular hypoplasia and the protrusion of thetongue. Both calves were traced back to the same sire,one of the breeding lines most recently used inHolsteins in Italy

Figure 14: Brown calf affected by Perosomus elumbis;note the brachygnathia of the lower jaw and the short-ened torso

Figure 15: Anatomical dissection of the same calf as inFig. 14; the lumbar, sacral and coccygeal vertebrae wereentirely lacking

Inherited disorders of cattle: A selected review 25

The skeletal anomaly is often accompanied byother endocavitary malformations (e.g. colon/rec-tum/anal atresia with a blind-ending-sac filledwith mucoid faeces and protruding at the level ofthe sacral region, renal agenesis, cardiac anom-alies) which make the situation incompatible withlife. The spinal cord ends in a blind vertebralcanal.

Malformation or improper migration of theneural tube during the tail-bud stage, accompa-nied by partial agenesis of the caudal spinal cord,seems to be the cause of this abnormality.

Syndactyly (Mule Foot) (60, 61, 62, 63)

Fusion or non-division of the digits constitutesa well known hereditary defect in Holstein cattlebut has been described in a number of other cat-tle breeds. The lesion is primarily osteological innature and consist mainly in synostotic pha-langes; more proximal limb structures can beaffected as well, such as metacarpal andmetatarsal III and IV bones. The syndactyloushoof has the aspect of a truncated cone with thebase at the coronary seam. In Holstein cattle,Mule Foot has been confirmed as a simple auto-somal recessive inherited defect; the gene respon-sible is located on the telomeric end of chromo-some 15. An incomplete penetrance is demon-strated by the variable expressivity of the disease,mainly due to an interesting right-left and front-rear gradient, meaning that the right front foot isaffected more often, followed by the left front (Fig.16), right rear and left rear foot.

Inherited skin defect

Ichthyosis (64, 65, 66, 67, 68)

Ichthyosis is a rare skin disease reported indifferent breeds and characterized by diffusecutaneous hyperkeratosis giving the skin anappearance similar to that of fish. Currently, twocongenital forms of ichthyosis are described incattle: ichthyosis fetalis and ichthyosis congenita.

Ichthyosis fetalis (bovine harlequin foetus) isthe most severe form of bovine Icihthyosis and isincompatible with life; the affected calves are still-born or die within a few days after birth. The skinis covered with large horny plates separated bydeep fissures, resembling a ‘leather cuirass’; hairis usually completely absent. The thick, inelasticskin causes eversion at mucocutaneous junc-tions, eclabium and ectropion. This form appearsto be similar to human harlequin ichthyosis (HI)where there are severe plate-like cutaneous for-mations which are diffused over the body result-ing in early neonatal death.

Ichthyosis congenita is the milder form of thedisease; affected calves tend to live longer.General physical health is good. The lesions arecharacterized by hyperkeratosis, present at birthor developing over several weeks; hairlessness isnot an initial feature, but alopecia may develop.Thick and large cutaneous scales are typical andmore severe over the limbs, abdomen and muzzle

Figure 16: Holstein calf affected by Syndactyly; only thefront legs show syndactylous hoof

Figure 17: Three-month-old female Chianina calf affect-ed by Ichtyosis congenita. Note the alopecic areas onthe muzzle, eyelids and ears. The areas were covered bythick, dark-grey, dry, scale-like hyperkeratotic material.The diameter of the scales was 2-3 mm

A. Gentile, S. Testoni26

(Fig. 17). Cataract, microtia and thyroid abnor-malities have been reported in calves affected withthis disorder. Bovine ichthyosis congenita resem-bles lamellar ichthyosis in humans (LI).

In both forms of ichthyosis, the constant histolog-ical feature, despite the variable anatomic sites andseverity, is the marked orthokeratotic lamellar hyper-keratosis of the epidermis and follicular epidermis.

Presumably, as in the human forms ofichthyosis, the scales are the product of a defec-tive desquamation associated with increasedcohesion of keratinocytes and therefore representa large number of cohesive corneocytes retainedand shed simultaneously.

Both forms of ichthyosis in cattle are thoughtto be inherited through a simple autosomal reces-sive gene. By comparative analysis with thehuman forms of ichthyosis, a research project isunderway at the University of Milan (Italy) wherethey are working on the candidate gene TGM1(keratinocyte transglutaminase 1), responsible inman for the activity of TGase1, an enzyme in thecornified cell envelope assembly line.

Since neither chromosomal nor biochemicaltests are yet available to detect carriers of thisdefect, reports of affected animals and the accu-rate identification of clinical cases are the onlyopportunity for carrier animals to be detected inretrospect.

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DEDNE BOLEZNI PRI GOVEDU: IZBRAN PREGLED

A. Gentile, S. Testoni

Povzetek: V goveji populaciji je zaradi visoke stopnje medsebojnega parjenja nevarnost pojavljanja genetskih obolenj.

Razširjena uporaba semena samo elitnih bikov poveča verjetnost pojavitve dveh mutiranih recesivnih genov v genotipu

enega potomca.

Znaki, ki nakazujejo, da je bolezenska sprememba verjetno genetskega izvora, so:

1. bolezensko stanje je pogostejše v skupini sorodnih živali

2. bolezensko stanje opažamo v vseh letnih časih in na različnih geografskih področjih

3. stanje postaja pogostejše, ko se pogostnost medsebojnega parjenja povečuje

V zadnjem času smo imeli izkušnje predvsem z genetskimi obolenji.

Dedne bolezni centralnega živčnega sistema: Mišična atrofija, ki izvira iz hrbtenjače, je najbolj zaskrbljujoča dedna hiba

sivorjavih telet, ki jo označuje huda mišična atrofija, progresivna pareza vseh okončin in ležanje na prsnici od tretjega ali

četrtega tedna dalje. Izguba mielina hrbtenjače je prirojena nevrološka motnja, ki prizadene predvsem teleta sivorjave

pasme. Ta po rojstvu ne morejo vstati in imajo tipično iztegnjene zadnje okončine. Prizadetost povzroča izguba mielina v

belini hrbtenjače. Goveja progresivna degenerativna mieloencefalopatija (sindrom "tkalca") je dedna motnja čistokrvne

sivorjave pasme. Zanjo je značilna progresivna šibkost zadnjih okončin in nekoordinirano gibanje, ki spominja na gibanje

rok pri uporabi tkalskega čolnička (weaver syndrome - sindrom tkalca). Klinični znaki postanejo očitni med 6. in 8. mese-

cem starosti. Spastična pareza je najbolj problematična dedna hiba pasme romagnola. Napaka se odraža v hipereksten-

ziji skočnega sklepa in nenormalnem gibanju zadnje okončine. V najhujših primerih je prizadeta okončina stalno iztegnje-

na in nenehni krči povzročajo tipično gibanje v obliki nihala. Znaki spastične pareze se pojavijo med 3. in 8. mesecem

starosti, ko spastični krči prizadenejo iztegovalke skočnega sklepa. Spastični sindrom je resen problem pri bikih v ose-

menjevalnih centrih, ki lahko prizadene tudi krave v progresivni ali ponavljajoči se obliki. Ponavljajoči se krči obojestransko

prizadenejo notranje ledvene in križno-ledvene mišice. Pojavi se kifoza in drhtenje zadnjih okončin. Sčasoma se inten-

zivnost in trajanje krčev povečujeta.

Podedovane prirojene napake skeleta: Hondrodisplazija je znana tudi pod imenom "bulldog" telet in je bila včasih pogos-

ta pri pasmi romagnola. Lobanja je sploščena, smrček kratek, čelo pa se le počasi vzdiguje. Prizadete živali imajo tudi kra-

jše okončine. Pri t. i. "prirojenem sindromu telečjega vampa" pasme romagnola poleg skrajšane in sploščene lobanje

Inherited disorders of cattle: A selected review 29

opazimo še volčje žrelo in napihnjenost trebuha zaradi znatno povečane količine tekočine v trebušni votlini. Kompleksna

nepravilnost vretenc (CVM - complex vertebral malformations) predstavlja najresnejšo dedno napako telet črno-bele

pasme. Teleta so manjša, imajo simetrično artrogripozo in popačeno obliko vratnih ali prsnih vretenc. Najpogosteje opaz-

imo skrajšan vrat in skoliozo. Anomalije na vretencih so lahko hemivretenca, združevanje vretenc med sabo in vretenc z

rebri, skrivljenost reber in nepravilne oblike na vretencih. Homozigoti pogosto poginejo že pred rojstvom. Arahnomelia je

prirojena napaka skeletnega sistema, ki daje novorojeni živali pajkast videz. Opisana je pri teletih sivorjave pasme in simen-

talcih. Deformirane so predvsem obrazne kosti in distalni deli zadnjih okončin, opisujemo tudi kostno dolihostenomelijo

(nenormalno dolge in tanke okončine). Kosti okončin so tudi bolj krhke in spontani zlomi med telitvijo lahko poškodujejo

kravo. Smrtonosno skrajšanje hrbtenice je redka napaka skeletnega sistema. Teleta so bistveno manjša in hrbtenica je

nesorazmerna. Vretenca so lahko združena, njihovo število je različno, samo telo vretenc pa je nepravilne oblike in velikosti.

V vratnem in prsno-ledvenem področju vretenca pogosto tudi niso poravnana. Perosomus acaudatus in Perosomus

elumbis sta izraza, ki označujeta nepopolno razvitost hrbtenice. Teletu lahko manjka le rep (Perosomus acaudatus) ali pa

tudi del križnega, celo ledvenega dela (Perosomus elumbis). Manjkajoči rep po navadi ne predstavlja nevarnosti za življen-

je, medtem ko teleta s Perosomus elumbis ne preživijo, saj manjka čvrsta opora za zadnje okončine, ki so pri tem stanju

tudi zelo nerazvite. Sindaktilija ("noga mule") je znana napaka, pri kateri so prsti združeni. Izraženost napake zelo variira.

Običajno so bolj prizadete sprednje okončine in desna stran bolj od leve.

Prirojene napake kože: Ihtioza je difuzna hiperkeratinizacija kože. Koža je podobna ribji, od tod ime. Poznamo dve obliki

ihtioze. Ichthyosis fetalis ali "goveji harlekin fetus" je prirojena in zelo resna napaka, ki ni združljiva z življenjem. Ichthyosis

congenita je milejša oblika in prizadete živali lahko živijo dlje. V obeh primerih je koža pokrita s velikimi bodičastimi ploskva-

mi, med katerimi so globoke zareze, kot nekakšen usnjen oklep.

Ključne besede: dedne bolezni; centralni živčni sistem, bolezni – genetika; kožne bolezni – genetika; kost, bolezni –

genetika; govedo